Certain disease of the respiratory tract are known to respond to treatment by the direct application of medicinal agents. As many such agents are most readily available as a finely divided material, e.g., in dry powdered form, their delivery is most conveniently accomplished by inhaling the finely divided material through the nose or mouth. This results in better utilization of the medicinal agent in that it is deposited exactly at the site desired and where its action may be required; hence, very minute doses of the therapeutic agent are often equally as efficacious as larger doses administered by other means, with a consequent marked reduction in the incidence of undesired side effects. Alternately, the therapeutic agent in this form may be used for treatment of diseases other than those of the respiratory system, for example, for the delivery of systemically absorbed medicaments such as insulin. When the drug is deposited on the very large surface areas of the respiratory tract, it may be very rapidly absorbed into the blood stream; hence, this method of application may take the place of administration by injection, tablet, or other conventional means.
A variety of inhalation devices for the delivery of finely divided materials are known in the art. For example, U.S. Pat. No. 4,240,418 discloses inhalation devices wherein a container of finely divided material is positioned so that the material from the container can pass by gravity to a delivery area of the device from which it is dispensed. Accordingly, these devices suffer the disadvantage that the use must maintain the device in a particular position so that the finely divided material can pass by gravity to the collecting plate and is not dislodged therefrom prior to dispensing. It appears that such devices also require a large dispensing passage to prevent interference with the free fall of a relatively large load of the finely divided material.
Other known inhalation devices incorporate a deflector (U.S. Pat. No. 4,098,273) or a hollow tube (U.S. Pat. No. 3,938,516) to divert air flow into a chamber to dislodge the finely divided material, thereby requiring a substantial flow of air to disperse the finely divided material. Inhalation sufficient to create such a substantial flow of air is difficult for some users, e.g., asthmatics. Furthermore, it is believed that such devices deliver somewhat imprecise doses due to the inevitable variations in residue of finely divided material left behind in the container after dispensing.
Some known inhalation devices use members which vibrate to dispense the finely divided material, thus increasing the complexity and bulk of the device. For example, the devices of U.S. Pat. No. 3,948,264, utilize batteries to activate vibrators. Other devices incorporate breath activated vibratable members to disperse the finely divided materials. See, e.g., U.S. Pat. Nos. 3,888,253 and 4,995,385 which include a member which vibrates in the airflow to dispense the finely divided material. Still other known devices use a breath activated propeller device to spin the container of finely divided material, thereby casting the material out by centrifugal force, e.g., U.S. Pat. No. 3,507,277. A relatively high velocity of air flow is required to activate such devices, again a problem for breath impaired users.
Moisture in most powders tends to cause agglomeration and clumping thereby inhibiting the breakup and dispersion of the finely divided medication, an essential step in effective dispensing of the material.
However, the manner in which many known devices operate renders hermetic sealing of the container of finely divided material impossible. In still other known devices, the containers for finely divided materials are gelatin capsules which are susceptible to atmospheric moisture.
Recently, inhalation devices have been developed which include an aerosol container housing a mixture of a propellant and a drug. See, e.g., U.S. Pat. Nos. 6,126,919, 6,120,752 and 6,054,488. Certain drugs cannot be successfully mixed with propellants. Further, such mixtures often result in agglomeration of the drug, degradation of the components, chemical instability, and limited shelf lives. In an attempt to solve these problems, certain additives such as, for example, cosolvents, surfactants and dispersants are often added. As a result, pure medicinal agent is not delivered. Further, with such devices, prior to each use, it is required to shake the device vigorously to ensure that the mixture of drug, cosolvents, surfactants, dispersants and other components are suspended in the propellant and to try to provide a uniform mixture of the components. Further, with such devices, it is important to keep track of how much medicine has been used so that the user replaces the device before running out of the medicine. One way this is done is for the user to write a refill date on the device. To figure out the refill date, a user must divide the number of puffs in the device (often, this number is printed the device) by the number of puffs the user takes each day. The resulting number is the number of days the device should last. The user than counts forward that many days to estimate the refill date. However, this process is inconvenient and is often inaccurate because it does not take into account days in which more or fewer puffs are taken.
New and more potent drugs which can be used in increasingly small quantities are being developed on an ongoing basis. In most instances, known inhalation devices for finely divided materials are not capable of delivering such small quantities without the addition of a significant amount of filler. It is highly desirable to minimize the use of such fillers, e.g., in order to reduce the likelihood of side effects.
It can be seen that presently known devices for the delivery of finely divided materials suffer disadvantages which include, among others, imprecise delivery, inability to deliver directly from a hermetically sealed container, agglomeration and clumping of the medicinal agents, reduced shelf life of the medicinal agents, chemical instability, inability to deliver small doses of pure medicinal agent, requirement of good coordination for use and high breath demands upon the user, requirement to shake the device to prevent settling of the medicinal agent, limited portability due to bulk, difficulty to keep track of how much medicinal agent has been used and how much remains and complexity of design. Thus, alternative inhalation devices are being sought.